Prostate cancer is the most common solid malignancy among men in the United States. African American men have the highest incidence of prostate cancer compared to other ethnic groups. This cohort also appears to present more commonly at an advanced stage with aggressive histology and increased cancer-related mortality. Thus, there is a critical need to explore the etiologic pathways (genetic and environmental factors) that contribute to this disparity. African Americans share a common genetic background with West Africans yet vastly different environments. Comparative genetic and epidemiological research on the two populations may reveal potential risk factors. This project seeks to provide a better understanding of gene-gene(epistasis), and gene- environment effects on prostate cancer. At research sites in Washington, DC, Baltimore, MD, and Monrovia, Liberia, the goals of this project are to (1) recruit a well characterized cohort of 800 cases and controls and collect blood for biochemical and molecular assays, along with diet and other environmental information; (2) use microarray technology to assess the expression of candidate genes in normal and cancer tissue from African and European Americans; (3) use state of the art DHPLC technology to provide a formal evaluation of single nucleotide polymorphism (SNP) variation in 22 candidate genes for prostate cancer (androgen associated genes, apoptosis related genes, and diet related genes); (4) genotype relevant SNPs within candidate genes and construct haplotypes; (5) develop a web-based database of the SNPs discovered and their allele frequencies; (6) determine if haplotypic variation in candidate genes account for phenotypic variation in prostate cancer, prostate specific antigen (PSA) levels, and disease progression; and (7) assess whether gene-gene and gene-environment interactions exist by examining if prostate cancer risk is modified after stratification of genetic and/or environmental factors.